{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:00:40Z","timestamp":1792512040931,"version":"4.5.0"},"reference-count":61,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T00:00:00Z","timestamp":1588204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR16-CE13-0005-01"],"award-info":[{"award-number":["ANR16-CE13-0005-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003323","name":"Agence Nationale de Recherches sur le Sida et les H\u00e9patites Virales","doi-asserted-by":"publisher","award":["ANRS2014-CI-2, ANRS2014-049, ANRS2018-2"],"award-info":[{"award-number":["ANRS2014-CI-2, ANRS2014-049, ANRS2018-2"]}],"id":[{"id":"10.13039\/501100003323","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007380","name":"Fondation de l'Avenir pour la Recherche M\u00e9dicale Appliqu\u00e9e","doi-asserted-by":"publisher","award":["FRM DEQ2016 0334894"],"award-info":[{"award-number":["FRM DEQ2016 0334894"]}],"id":[{"id":"10.13039\/100007380","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004412","name":"Human Frontier Science Program","doi-asserted-by":"publisher","award":["RGP0035\/2016"],"award-info":[{"award-number":["RGP0035\/2016"]}],"id":[{"id":"10.13039\/100004412","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>HIV-1 infection is frequently associated with low bone density, which can progress to osteoporosis leading to a high risk of fractures. Only a few mechanisms have been proposed to explain the enhanced osteolysis in the context of HIV-1 infection. As macrophages are involved in bone homeostasis and are critical host cells for HIV-1, we asked whether HIV-1-infected macrophages could participate in bone degradation. Upon infection, human macrophages acquired some osteoclast features: they became multinucleated, upregulated the osteoclast markers RhoE and \u03b23 integrin, and organized their podosomes as ring superstructures resembling osteoclast sealing zones. However, HIV-1-infected macrophages were not fully differentiated in osteoclasts as they did not upregulate NFATc-1 transcription factor and were unable to degrade bone. Investigating whether infected macrophages participate indirectly to virus-induced osteolysis, we showed that they produce RANK-L, the key osteoclastogenic cytokine. RANK-L secreted by HIV-1-infected macrophages was not sufficient to stimulate multinucleation, but promoted the protease-dependent migration of osteoclast precursors. In conclusion, we propose that, by stimulating RANK-L secretion, HIV-1-infected macrophages contribute to create a microenvironment that favors the recruitment of osteoclasts, participating in bone disorders observed in HIV-1 infected patients.<\/jats:p>","DOI":"10.3390\/ijms21093154","type":"journal-article","created":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T03:18:19Z","timestamp":1588216699000},"page":"3154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["HIV-1-Infected Human Macrophages, by Secreting RANK-L, Contribute to Enhanced Osteoclast Recruitment"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7009-2786","authenticated-orcid":false,"given":"R\u00e9mi","family":"Mascarau","sequence":"first","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, Universit\u00e9 de Toulouse, CNRS UMR 5089, Universit\u00e9 Toulouse III Paul Sabatier, CEDEX 04, 31077 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florent","family":"Bertrand","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, Universit\u00e9 de Toulouse, CNRS UMR 5089, Universit\u00e9 Toulouse III Paul Sabatier, CEDEX 04, 31077 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Labrousse","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, Universit\u00e9 de Toulouse, CNRS UMR 5089, Universit\u00e9 Toulouse III Paul Sabatier, CEDEX 04, 31077 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8572-7852","authenticated-orcid":false,"given":"Isabelle","family":"Gennero","sequence":"additional","affiliation":[{"name":"Centre de Physiopathologie de Toulouse-Purpan, INSERM-CNRS UMR 1043, Universit\u00e9 Toulouse III Paul Sabatier, 31024 Toulouse, France"},{"name":"Institut F\u00e9d\u00e9ratif de Biologie, Centre Hospitalier Universitaire Toulouse, 31059 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2884-1744","authenticated-orcid":false,"given":"Renaud","family":"Poincloux","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, Universit\u00e9 de Toulouse, CNRS UMR 5089, Universit\u00e9 Toulouse III Paul Sabatier, CEDEX 04, 31077 Toulouse, France"},{"name":"International Associated Laboratory (LIA) CNRS \u201cIM-TB\/HIV\u201d (1167), 31077 Toulouse, France"},{"name":"International Associated Laboratory (LIA) CNRS \u201cIM-TB\/HIV\u201d (1167), Buenos Aires C1425AUM, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Maridonneau-Parini","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, Universit\u00e9 de Toulouse, CNRS UMR 5089, Universit\u00e9 Toulouse III Paul Sabatier, CEDEX 04, 31077 Toulouse, France"},{"name":"International Associated Laboratory (LIA) CNRS \u201cIM-TB\/HIV\u201d (1167), 31077 Toulouse, France"},{"name":"International Associated Laboratory (LIA) CNRS \u201cIM-TB\/HIV\u201d (1167), Buenos Aires C1425AUM, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Raynaud-Messina","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, Universit\u00e9 de Toulouse, CNRS UMR 5089, Universit\u00e9 Toulouse III Paul Sabatier, CEDEX 04, 31077 Toulouse, France"},{"name":"International Associated Laboratory (LIA) CNRS \u201cIM-TB\/HIV\u201d (1167), 31077 Toulouse, France"},{"name":"International Associated Laboratory (LIA) CNRS \u201cIM-TB\/HIV\u201d (1167), Buenos Aires C1425AUM, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1079-9085","authenticated-orcid":false,"given":"Christel","family":"V\u00e9rollet","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie et Biologie Structurale, Universit\u00e9 de Toulouse, CNRS UMR 5089, Universit\u00e9 Toulouse III Paul Sabatier, CEDEX 04, 31077 Toulouse, France"},{"name":"International Associated Laboratory (LIA) CNRS \u201cIM-TB\/HIV\u201d (1167), 31077 Toulouse, France"},{"name":"International Associated Laboratory (LIA) CNRS \u201cIM-TB\/HIV\u201d (1167), Buenos Aires C1425AUM, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1097\/COH.0000000000000028","article-title":"The effects of untreated and treated HIV infection on bone disease","volume":"9","author":"Cotter","year":"2014","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s40506-017-0109-9","article-title":"Bone Loss in HIV Infection","volume":"9","author":"Moran","year":"2017","journal-title":"Curr. Treat. Options Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1097\/00002030-200309050-00010","article-title":"Decreased bone mineral density in HIV-infected patients is independent of antiretroviral therapy","volume":"17","author":"Bruera","year":"2003","journal-title":"Aids"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1002\/jmv.20938","article-title":"RANK-L\/OPG\/TRAIL plasma levels and bone mass loss evaluation in antiretroviral naive HIV-1-positive men","volume":"79","author":"Gibellini","year":"2007","journal-title":"J. Med. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1097\/QAD.0b013e32833c93fe","article-title":"High prevalence of reduced bone mineral density in primary HIV-1-infected men","volume":"24","author":"Grijsen","year":"2010","journal-title":"Aids"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Titanji, K., Vunnava, A., Sheth, A.N., Delille, C., Lennox, J.L., Sanford, S.E., Foster, A., Knezevic, A., Easley, K.A., and Weitzmann, M.N. (2014). Dysregulated B cell expression of RANK-L and OPG correlates with loss of bone mineral density in HIV infection. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004497"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1111\/acel.12308","article-title":"The HIV proteins Tat and Nef promote human bone marrow mesenchymal stem cell senescence and alter osteoblastic differentiation","volume":"14","author":"Beaupere","year":"2015","journal-title":"Aging Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1002\/jor.22196","article-title":"HIV-1 protein induced modulation of primary human osteoblast differentiation and function via a Wnt\/\u03b2-catenin-dependent mechanism","volume":"31","author":"Butler","year":"2013","journal-title":"J. Orthop. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1002\/jmv.21266","article-title":"HIV-1 triggers apoptosis in primary osteoblasts and HOBIT cells through TNFalpha activation","volume":"80","author":"Gibellini","year":"2008","journal-title":"J. Med. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/s41586-019-1105-7","article-title":"Developmental origin, functional maintenance and genetic rescue of osteoclasts","volume":"568","author":"Percin","year":"2019","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"605","DOI":"10.4049\/jimmunol.1201345","article-title":"Systemic circulation and bone recruitment of osteoclast precursors tracked by using fluorescent imaging techniques","volume":"190","author":"Kotani","year":"2013","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.1749-6632.2011.06283.x","article-title":"The osteoclast and its unique cytoskeleton","volume":"1240","author":"Teitelbaum","year":"2011","journal-title":"Ann. NY Acad. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1126\/science.289.5484.1504","article-title":"Bone resorption by osteoclasts","volume":"289","author":"Teitelbaum","year":"2000","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"191","DOI":"10.4161\/cam.27840","article-title":"Podosome organization drives osteoclast-mediated bone resorption","volume":"8","author":"Georgess","year":"2014","journal-title":"Cell Adh. Migr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1002\/jbmr.3092","article-title":"RANK-L-Independent Osteoclastogenesis: A Long-Standing Controversy","volume":"32","author":"Tanaka","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"179","DOI":"10.4161\/cam.28116","article-title":"Podosomes in space: Macrophage migration and matrix degradation in 2D and 3D settings","volume":"8","author":"Wiesner","year":"2014","journal-title":"Cell Adh. Migr."},{"key":"ref_17","first-page":"203","article-title":"The molecular dynamics of osteoclast adhesions. Eur","volume":"85","author":"Luxenburg","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1091\/mbc.e13-07-0363","article-title":"Comparative transcriptomics reveals RhoE as a novel regulator of actin dynamics in bone-resorbing osteoclasts","volume":"25","author":"Georgess","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1007\/s00774-016-0749-8","article-title":"Bone metabolism dysfunction mediated by the increase of proinflammatory cytokines in chronic HIV infection","volume":"35","author":"Machado","year":"2017","journal-title":"J. Bone Miner. Metab"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s11904-011-0099-z","article-title":"HIV: Inflammation and bone","volume":"9","author":"Ofotokun","year":"2012","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1097\/QAD.0000000000001764","article-title":"T-cell receptor activator of nuclear factor-kappaB ligand\/osteoprotegerin imbalance is associated with HIV-induced bone loss in patients with higher CD4+ T-cell counts","volume":"32","author":"Titanji","year":"2018","journal-title":"AIDS"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13848","DOI":"10.1073\/pnas.1003020107","article-title":"Alterations in the immuno-skeletal interface drive bone destruction in HIV-1 transgenic rats","volume":"107","author":"Vikulina","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12977-015-0139-7","article-title":"HIV-1 replicates in human osteoclasts and enhances their differentiation in vitro","volume":"12","author":"Gohda","year":"2015","journal-title":"Retrovirology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8282","DOI":"10.1038\/ncomms9282","article-title":"Role of T-cell reconstitution in HIV-1 antiretroviral therapy-induced bone loss","volume":"6","author":"Ofotokun","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_25","first-page":"E2556","article-title":"Bone degradation machinery of osteoclasts: An HIV-1 target that contributes to bone loss","volume":"115","author":"Bracq","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7431","DOI":"10.1073\/pnas.1818662116","article-title":"Inhibition of the lncRNA SAF drives activation of apoptotic effector caspases in HIV-1-infected human macrophages","volume":"116","author":"Boliar","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/s41590-018-0085-3","article-title":"Resistance of HIV-infected macrophages to CD8(+) T lymphocyte-mediated killing drives activation of the immune system","volume":"19","author":"Clayton","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/s41564-018-0335-z","article-title":"HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy","volume":"4","author":"Ganor","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.3389\/fimmu.2017.01698","article-title":"Myeloid Cell Interaction with HIV: A Complex Relationship","volume":"8","author":"Rodrigues","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1182\/blood-2014-08-596775","article-title":"HIV-1 reprograms the migration of macrophages","volume":"125","author":"Souriant","year":"2015","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.chom.2016.02.013","article-title":"Macrophages and HIV-1: An Unhealthy Constellation","volume":"19","author":"Sattentau","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s11914-017-0384-x","article-title":"Osteomacs and Bone Regeneration","volume":"15","author":"Batoon","year":"2017","journal-title":"Curr. Osteoporos Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.biomaterials.2017.10.033","article-title":"CD169(+) macrophages are critical for osteoblast maintenance and promote intramembranous and endochondral ossification during bone repair","volume":"196","author":"Batoon","year":"2019","journal-title":"Biomaterials"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s00424-017-1952-8","article-title":"Latest perspectives on macrophages in bone homeostasis","volume":"469","author":"Bozec","year":"2017","journal-title":"Pflugers Arch."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/s41586-019-1471-1","article-title":"Locally renewing resident synovial macrophages provide a protective barrier for the joint","volume":"572","author":"Culemann","year":"2019","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4029","DOI":"10.1182\/blood-2004-01-0041","article-title":"Immature dendritic cell transdifferentiation into osteoclasts: A novel pathway sustained by the rheumatoid arthritis microenvironment","volume":"104","author":"Rivollier","year":"2004","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5074","DOI":"10.1182\/blood-2008-01-132787","article-title":"Bone marrow microenvironment controls the in vivo differentiation of murine dendritic cells into osteoclasts","volume":"112","author":"Wakkach","year":"2008","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1016\/j.drudis.2016.04.022","article-title":"Dendritic-cell-derived osteoclasts: A new game changer in bone-resorption-associated diseases","volume":"21","author":"Laperine","year":"2016","journal-title":"Drug Discov. Today"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7030","DOI":"10.4049\/jimmunol.0903345","article-title":"HIV-1 Nef triggers macrophage fusion in a p61Hck- and protease-dependent manner","volume":"184","author":"Zhang","year":"2010","journal-title":"J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1007\/s11481-011-9298-z","article-title":"Human immunodeficiency virus type 1 endocytic trafficking through macrophage bridging conduits facilitates spread of infection","volume":"6","author":"Kadiu","year":"2011","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.chom.2014.10.010","article-title":"Macrophage Infection via Selective Capture of HIV-1-Infected CD4(+) T Cells","volume":"16","author":"Baxter","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.ejcb.2005.09.008","article-title":"Podosome and sealing zone: Specificity of the osteoclast model","volume":"85","author":"Jurdic","year":"2006","journal-title":"Eur. J. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1242\/jcs.202036","article-title":"Time-lapse reveals that osteoclasts can move across the bone surface while resorbing","volume":"130","author":"Soe","year":"2017","journal-title":"J. Cell Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3649","DOI":"10.1242\/jcs.108.12.3649","article-title":"Matrix metalloproteinases are obligatory for the migration of preosteoclasts to the developing marrow cavity of primitive long bones","volume":"108","author":"Blavier","year":"1995","journal-title":"J. Cell Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3608","DOI":"10.1096\/fj.13-232736","article-title":"Hck contributes to bone homeostasis by controlling the recruitment of osteoclast precursors","volume":"27","author":"Gallois","year":"2013","journal-title":"FASEB J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1158\/2326-6066.CIR-17-0746","article-title":"The Protease-Dependent Mesenchymal Migration of Tumor-Associated Macrophages as a Target in Cancer Immunotherapy","volume":"6","author":"Gui","year":"2018","journal-title":"Cancer Immunol. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.4049\/jimmunol.0902223","article-title":"Matrix Architecture Dictates Three-Dimensional Migration Modes of Human Macrophages: Differential Involvement of Proteases and Podosome-Like Structures","volume":"184","author":"Poincloux","year":"2010","journal-title":"J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.pharmthera.2017.02.017","article-title":"Macrophages and skeletal health","volume":"174","author":"Michalski","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1016\/j.bone.2008.08.128","article-title":"Osteal macrophages: A new twist on coupling during bone dynamics","volume":"43","author":"Pettit","year":"2008","journal-title":"Bone"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1111\/j.1600-0854.2005.00307.x","article-title":"Activation of the lysosome-associated p61Hck isoform triggers the biogenesis of podosomes","volume":"6","author":"Cougoule","year":"2005","journal-title":"Traffic"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1091\/mbc.e07-03-0227","article-title":"The tyrosine kinase activity of c-Src regulates actin dynamics and organization of podosomes in osteoclasts","volume":"19","author":"Destaing","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4878","DOI":"10.1242\/jcs.03271","article-title":"Involvement of the Src-cortactin pathway in podosome formation and turnover during polarization of cultured osteoclasts","volume":"119","author":"Luxenburg","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1196\/annals.1402.071","article-title":"The role of NFAT in osteoclast formation","volume":"1116","author":"Takayanagi","year":"2007","journal-title":"Ann. NY Acad. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S1534-5807(02)00369-6","article-title":"Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANK-L signaling in terminal differentiation of osteoclasts","volume":"3","author":"Takayanagi","year":"2002","journal-title":"Dev. Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"987","DOI":"10.2353\/ajpath.2006.060180","article-title":"B and T lymphocytes are the primary sources of RANK-L in the bone resorptive lesion of periodontal disease","volume":"169","author":"Kawai","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_56","first-page":"731039","article-title":"RANK-L expression in periodontal disease: Where does RANK-L come from?","volume":"2014","author":"Chen","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_57","first-page":"17","article-title":"Expression of RANK-L and OPG mRNA in periodontal disease: Possible involvement in bone destruction","volume":"11","author":"Liu","year":"2003","journal-title":"Int. J. Mol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/978-0-387-72009-8_2","article-title":"Ectodomain shedding of receptor activator of NF-kappaB ligand","volume":"602","author":"Hikita","year":"2007","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7070","DOI":"10.1073\/pnas.0304859101","article-title":"HIV-1-mediated apoptosis of neuronal cells: Proximal molecular mechanisms of HIV-1-induced encephalopathy","volume":"101","author":"Xu","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3586","DOI":"10.1016\/j.celrep.2019.02.091","article-title":"Tuberculosis Exacerbates HIV-1 Infection through IL-10\/STAT3-Dependent Tunneling Nanotube Formation in Macrophages","volume":"26","author":"Souriant","year":"2019","journal-title":"Cell Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4028","DOI":"10.1021\/acsnano.7b00622","article-title":"Podosome Force Generation Machinery: A Local Balance between Protrusion at the Core and Traction at the Ring","volume":"11","author":"Bouissou","year":"2017","journal-title":"ACS Nano"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/9\/3154\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:24:09Z","timestamp":1760361849000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/9\/3154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,30]]},"references-count":61,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["ijms21093154"],"URL":"https:\/\/doi.org\/10.3390\/ijms21093154","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.737901608.793584009","asserted-by":"object"}]},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,30]]}}}